Historically, human and animal vaccines have been limited to formulations containing attenuated or killed pathogen. While effective for preventing a subset of diseases in both humans and animals, there are a number of drawbacks associated with the production of pathogen-based vaccines. For example, production can be limited due to difficulty in culturing the pathogen in question and, even if successful, the process can be slow and laborious (e.g., manufacturing flu vaccines in eggs). This can restrict mobilization of vaccine manufacturing in response to newly emerging pathogens. Further, safety is a consistent and major concern for pathogen-based vaccines as a result of the possibility that attenuated vaccines can undergo mutation or recombination in the host leading to restoration of virulence or, in the case of killed-pathogens, the possibility that not all pathogens in a given formulation have been inactivated. Alternative formulations in the form of recombinant sub-unit vaccines have also proven problematic because sub-unit based approaches commonly fail to elicit “danger signals” associated with whole killed or attenuated pathogens. This failure results in a reduced immune response and a minimization of antigen effectiveness.
Therefore, there remains a need in the art for improved methods for rapid, high-fidelity and cost-effective production and purification of recombinant polypeptides and recombinant sub-unit vaccines. This invention addresses this need.